DESCRIPTION: (Applicant's Abstract) The long-term objectives of this research are to employ a cognitive neuropsychological model to conceptualize the effects of HIV and club drug abuse on the brain, to relate these effects to critical behaviors such as high risk sexual and injection practices in HIV-seropositive and seronegative men who have sex with men (MSMs), and to obtain preliminary data on the relationship between these effects and adherence with antiretroviral therapy. The abuse of MDMA ("Ecstasy'), ketamine ("Special K") and other club drugs is on the rise among MSMs and evidence indicates that the majority of club drugs have known or potential neurotoxic effects; however, neurocognition and club drug use has not been studied in MSMs or in the context of HIV infection. HIV infection and abuse of MDMA, the most common club drug of abuse among MSMs, cause dysfunction in overlapping frontal-subcortical brain regions. This study will evaluate the question of whether a history of MDMA abuse in the context of HIV infection will increase vulnerability to neurocognitive deficits, a question with significant potential diagnostic and therapeutic implications. We assume that careful study of specific cognitive functions mediated by different frontal-subcortical circuits will permit characterization of HIV-related cognitive impairment and its manifestation in persons who abuse MDMA. The specific aims of this investigation are to compare the performance of HIV-seropositive (HIV+) and HIV-seronegative (HIV-) MSMs with a current or past history of MDMA abuse and control groups of HIV+ and HIV- MSMs with no history of MDMA abuse on measures of decision-making, working memory, response inhibition and prospective memory, "executive" functions dependent on the integrity of prefrontal-subcortical pathways and potential mechanisms of HIV-related cognitive dysfunction; to evaluate the association of HIV serostatus and MDMA abuse with executive functions and sexual and drug use-related risk behavior; and to obtain preliminary data on levels of adherence with antiretroviral therapy in HIV+ MSMs with and without a history of MDMA abuse. The study will evaluate cognitive function in these groups employing state of the art computerized measures developed to model specific impairments associated with dysfunction of frontal-subcortical circuits. Data from the proposed study will advance knowledge of cognitive aspects of HIV-1 infection in the context of MDMA abuse; the practical implications of how cognitive impairment associated with HIV and club drug abuse influences behavior; and recent attempts to bridge the gap on how specific cognitive impairment can influence risk behavior and medication and adherence.